When xenobiotics are present in the water, a number of environmental factors affect their toxicity to fish. Important factors are temperature, pH for weak electrolytes, dissolved oxygen concentration, salinity, and induction of metabolizing enzymes. It is hypothesized that these factors affect toxicity primarily by affecting the kinetics of accumulation of xenobiotic from solution. To test this hypothesis, it is proposed that pharmacokinetic models be developed for the accumulation by Cyprinodon variegatus of four xenobiotics that are common pollutants of water: pentachlorophenol, trifluralin, di-2-ethylhexyl phthalate, and parathion. The models will be developed by placing fish in a solution of each xenobiotic and periodically determining the amount of xenobiotic in the fish and the total amount of metabolites formed. The models will yield rate constants and volumes of distribution; each parameter will reflect the kinetics of each step in the accumulation process; viz, uptake, distribution, and elimination. It is further proposed that the model parameters be determined over the temperature range 10 to 35 degrees, the dissolved oxygen concnetration range of 1.5 to 6.0 mcg/ml, the pH range (for weak electrolytes) of 5.4 to 9.4, salinity range of 5 to 20 mg/ml NaCl equivalents, and after induction of metabolizing enzymes. Finally, the median toxic level (TLm) of each xenobiotic will be determined under each of these conditions, and attempts will be made to relate this external measure of toxicity to an internal measure; i.e., total body concentration of xenobiotic or concentration in body water. The results of the proposed studies will provide new knowledge about the role of the pharmacokinetics of accumulation as a determinant of the toxicity of xenobiotics to fish.